Regional differences of energetics, mechanics, and kinetics of myosin cross-bridge in human ureter smooth muscle

This study provides information about baseline mechanical properties of the entire muscle and the molecular contractile mechanism in human ureter smooth muscle and proposed to investigate if changes in mechanical motor performance in different regions of isolated human ureter are attributable to differences in myosin crossbridge interactions. Classic mechanical, contraction and energetic parameters derived from the tension-velocity relationship were studied in ureteral smooth muscle strips oriented longitudinally and circularly from abdominal and pelvic human ureter parts. By applying of Huxley’s mathematical model we calculated the total working crossbridge number per mm2 (Ψ), elementary force per single crossbridge (Π0), duration of maximum rate constant of crossbridge attachment 1/f1 and detachment 1/g2 and peak mechanical efficiency (Eff.max). Abdominal longitudinal smooth muscle strips exhibited significantly higher maximum isometric tension and faster maximum unloaded shortening velocity compared to pelvic ones. Contractile differences were associated with significantly higher crossbridge number per mm2. Abdominal longitudinal muscle strips showed a lower duration of maximum rate constant of crossbridge attachment and detachment and higher peak mechanical efficiency than pelvic ones. Such data suggest that the abdominal human ureter showed better mechanical motor performance mainly related to a higher crossbridge number and crossbridge kinetics differences. Such results were more evident in the longitudinal rather than in the circular layer

Original Article Regional differences of energetics, mechanics, and kinetics of myosin cross-bridge in human ureter smooth muscle

Abstract: This study provides information about baseline mechanical properties of the entire muscle and the molecular contractile mechanism in human ureter smooth muscle and proposed to investigate if changes in mechanical motor performance in different regions of isolated human ureter are attributable to differences in myosin crossbridge interactions. Classic mechanical, contraction and energetic parameters derived from the tension-velocity relationship were studied in ureteral smooth muscle strips oriented longitudinally and circularly from abdominal and pelvic human ureter parts. By applying of Huxley's mathematical model we calculated the total working crossbridge number per mm 2 (Ψ), elementary force per single crossbridge (Π 0 ), duration of maximum rate constant of crossbridge attachment 1/f 1 and detachment 1/g 2 and peak mechanical efficiency (Eff. max ). Abdominal longitudinal smooth muscle strips exhibited significantly higher maximum isometric tension and faster maximum unloaded shortening velocity compared to pelvic ones. Contractile differences were associated with significantly higher crossbridge number per mm 2 . Abdominal longitudinal muscle strips showed a lower duration of maximum rate constant of crossbridge attachment and detachment and higher peak mechanical efficiency than pelvic ones. Such data suggest that the abdominal human ureter showed better mechanical motor performance mainly related to a higher crossbridge number and crossbridge kinetics differences. Such results were more evident in the longitudinal rather than in the circular layer

Bioactive Marine Natural Products: Isolation, Structure Elucidation and Synthesis

Marine sponges are a rich source of bioactive compounds which play an important role as protection against predators, overgrowing space competitors, invading microorganisms, and others. Over the past three decades, several biologically active secondary metabolites have been isolated from marine sponges and used to design and develop new therapeutic agents. The work described in this thesis addresses this research topic: the aim is to identify new chemical structures from marine organisms to be used as leads or scaffolds for the elaboration of new drugs. In particular, this PhD thesis consists of two main research activities: - Isolation and structural determination of new bioactive metabolites from marine sponges (Tedania ignis, Pseudaxinella flava and Plakortis simplex); - Synthesis of an analogue of simplexide, a glycolipid with an important immunoregulatory role. The results obtained from the chemical and pharmacological characterization of the new bioactive metabolites from marine sponges are here summarized: 1.00 2.00 3.00 The second line of research concerns a project focused on the synthesis of an analogue of simplexide, a glycolipid isolated from the Caribbean sponge Plakortis simplex in the year 1999. The simplexide showed to be a potent stimulus for the production of cytokines and chemokines, with interesting perspectives to be used in cancer and autoimmune diseases. In order to better understand the mechanism of action on immune system, the synthesis of a simpler analogue, having only a sugar in the saccharide chain, was carried out. Several synthetic approaches were applied, focusing on β-glycosilation step. The reactions were performed using conventional and microwave heating. Although the yields need further optimizations, the amount of the analogue of simplexide obtained so far will be tested on human blood monocytes

Potent anti-tumor and anti-inflammatory lead structures from Caribbean sponges

Marine natural products are playing an increasingly important role in biomedical research and drug discovery, either directly as drugs or as lead structures. Caribbean marine sponges are well-known to produce a large array of new chemical structures with promising anti-cancer, anti-inflammatory, immunomodulating and anti-bacterial properties. Over the last 15 years our research group’s interest has been focused on the chemical study of these colorful animals living in the tropical oceans as a source of new structures to be used as leads in the search of new drugs. Two topics of our ongoing research work will be discussed in the communication: a. the antinflammatory activity of tedanol, a new brominated and sulphated diterpene alcohol having a pimarane skeleton, which was isolated from the Caribbean sponge T. ignis. Tedanol showed a significant anti-inflammatory in vivo activity at 1 mg/kg, coupled with the inhibition of the COX-2 expression. This activity makes tedanol a novel potent COX-2 selective inhibitor, and could represent an excellent water-soluble antiinflammatory molecule with minimal gastrointestinal toxicity. b. The anti-tumor activity of three diterpene isonitriles isolated from the Caribbean sponge Pseudaxinella flava. The compounds have been first screened for their in vitro growth inhibitory activity (MTT assay) using the four human cell lines. Then, the gross mechanism of action of the isonitriles have been determined by means of computer-assisted phase contrast videomicroscopy analysis. The digital movies showed that the cancer cells treated with isonitriles are pro-autophagic agents and make the cells unable to undergo mitotic processes, resulting in a cytostatic effect

A new inositol-hopanoid from an Indonesian specimen of the sponge Plakortis simplex

During the past years, the Caribbean sponge Plakortis simplex has been extensively studied by our group, and bewildering variety of unusual glycolipids and other amphiphilic compounds have been isolated, including simplexide, discoside, plakoside, and 12-methylbacteriohopanetetrol. Recently, we had occasion to analyze for glycolipids an Indonesian specimen of P. simplex. In spite of the geographical distance, we found that the glycolipids composition of the Indonesian and Caribbean specimens were very similar. However, the Indonesian P. simplex also contained a new glycolipid, combining structural features of hopanoids and discoside, whose structure elucidation will be described

New Cyclic Diarylheptanoids from the Marine Sponge Tedania ignis

Diarylheptanoids (DHs) are a class of natural products mainly found in terrestrial plants of the families Betulaceae, Aceraceae, Myricaceae, Zingiberaceae and Dioscoreaceae. They have been reported to have various biological activities, including leishmanicidal and antiprotozoal, antitumor, antioxidant, anti-ischemic, anti-inflammatory, and inhibitory against nitric oxide production. In addition to the more common linear DHs, there are a smaller number of cyclic diarylheptanoids, which are formed from the corresponding linear type by phenolic oxidative coupling, either C–C coupling leading to meta,meta-bridged biaryls, or C–O coupling leading to bridged biaryl ethers. The isolation and structural elucidation of new cyclic diarylheptanoids (e.g. the diaryl ether 1) from the marine sponge Tedania ignis will be presented. This represents the first report of diarylheptanoids from marine organisms. Structure of compound 1 was established by NMR spectroscopy and ESI mass spectrometry. The NMR studies, carried out at temperatures comprised between 80°C and -70°C, demonstrated that the compound is present as a mixture of two slowly interconvertible enantiomeric confomers

A new inositol-hopanoid from an Indonesia specimen of the sponge Plakortis simplex

The Caribbean sponge Plakortis simplex has been extensively studied by our group, and a large variety of unusual glycolipids and other amphiphilic compounds have been isolated, including simplexide, discoside, and 12-methylbacteriohopanetetrol .Recently, we had occasion to analyze for glycolipids an Indonesian specimen of P. simplex. In spite of the geographical distance, we found that the glycolipids composition of the Indonesian and Caribbean specimens were very similar. However, the Indonesian P. simplex also contained a new glycolipid, combining structural features of hopanoids and discoside, whose structure elucidation will be described

CO2 Capture by Aqueous 3-(Methylamino)propylamine in Blend with Tertiary Amines: An NMR Analysis

Aqueous 3-(Methylamino)propylamine (MAPA) in blend with 2-(Diethylamino)ethanol (DEEA) and other tertiary amines, which mainly differ from DEEA in the number of hydroxyl functions (-OH) and/or in the length and structure of their alkyl chain, are investigated. After absorption of carbon dioxide (CO2) at 40 °C, quantitative 13C NMR experiments are performed to calculate the concentration of the species in each blend at equilibrium, together with qualitative NMR experiments for signal assignment. Speciation and absorption capacity data are discussed in terms of chemical structure and basicity of the tertiary amines. In general, it is observed that, at increasing pKa of the tertiary amines (decreasing number of –OH on the structure), there is a decrease of MAPA and primary and secondary MAPA carbamates, and an increase of MAPA dicarbamate, (bi)carbonate and of the absorption capacity. Within the molecules with the same number of –OH but differently branched, some exceptions are found